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Radioactive Nanocomposite Mouse Tumor Treatment

M.K. Khan, S.S. Nigavekar, L. Minc, B.M. Nair, M.S.T. Kariapper, W.G. Lesniak and L.P. Balogh
Roswell Park Cancer Institute, US

nanocomposite, gold, radiation therapy, cancer, melanoma

Nanocomposites have exciting potential medical uses, including cancer imaging and therapy (publications all in full abstract). Their design permits host and guest properties to be individually modified/optimized. The host component consists of poly(amidoamine) dendrimer polymers of discrete sizes, and regulated surface charges. The guest in this study is metallic gold (Au). We have previously published quantitative biodistribution analysis of non-targeted and folate targeted dendrimer nanoparticles (host only) in mouse tumor model systems, and showed that nanocomposites (guest + host) have very different biodistribution properties than the dendrimer (host only) nanodevices.
In this study radioactive (198Au(0)} nanocomposite devices were injected intra-tumorally into B16 melanoma (500 cubic mm) carrying mice and tumor volumes recorded over time. The four types of injections included: a) PBS buffer control, b) 30 uCi, c) 48 uCi, or d) nonradioactive control gold positive surface nanocomposites. There was statistically significant reduction of tumor growth (over 40%) in animals treated with radioactive 48 uCi (198Au(0)} nanocomposite devices, compared to PBS or nonradioactive (Au(0)} nanodevice treated animals (p=0.029, p=0.030 respectively). The dose level needed to produce tumor growth inhibition is consistent with dose levels achievable by targeted therapies. Our proof-of-principle results open the way for development of targeted nanocomposite radiotherapy.

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